New model of leukocyte arrest

Researchers at Israel's Weizmann Institute of Science report that lymphocytes rolling on high endothelial venules stop abruptly in response to chemokines presented by endothelial cells.¹ Their findings suggest that chemokines stop lymphocytes in a fraction of a second, faster than previously thought.

Ronen Alon and colleagues found that chemokines trigger instantaneous extension of the LFA-1 integrin – an adhesion molecule that changes between an inactive, bent conformation and an active, extended conformation. "The chemokine-mediated extension generates an intermediate affinity form of LFA-1, which brings the integrin head piece into close proximity with the adhesion molecule ICAM-1," says Alon. "Then, ICAM-1 triggers the conversion to high affinity."

Their physiological and biochemical data suggest that integrin activation happens in 0.1 to 0.5 seconds. They propose that the chemokine activation process of the LFA-1 integrin is "biconditional," involving both inside-out (intracellular to extracellular signaling) and outside-in (extracellular to intracellular signaling) conformational arrangements...